Correlation of Wilms' Tumor 1 Isoforms with HER2 and ER-α and its Oncogenic Role in Breast Cancer

Background: Wilms' tumor 1 (WT1) gene has different functional properties depending on the isoform type. This gene correlates with cell proliferation in various types of cancer. Here, we investigated the expression of WT1 isoforms in breast cancer tissues, and focused on the oncogenic role through estrogen receptor-alpha (ER-alpha) and human epidermal growth factor receptor 2 (HER2). Materials and Methods: Expression of WT1(17AA+) and (17AA-) was investigated in adjacent normal breast and breast cancer using Reverse transcription-polymerase chain reaction and western blotting. The correlation of WT1 isoforms with HER2 and ER-alpha was examined using MCF-7 cells stably-overexpressing WT1s and siRNA against WT1 gene. Results: The expression of WT(17AA-) was significantly found in adjacent normal breast tissues. A mixture of WT1(17AA+) and WT1(17AA-) were highly expressed in breast carcinoma tissues. MCF-7 cells overexpressing WT1+/+ and WT1+/- represented strong expression of ER-alpha and HER2. Moreover, the silencing of WT1+/+ and WT1+/- resulted in a decrease of both ER-alpha and HER2 and led to a decrease of cell numbers. Conclusion: Our results suggest that WT1(17AA+) was exhibited dominantly in breast carcinoma tissues. WT1+/+ and WT1+/- correlated with the high expression of ER-alpha and HER2, leading to cell proliferation and might be involved in cancer development and progression.